Selective Plane Illumination Microscopy (SPIM) is a technology that employs generation of a light sheet to illuminate a sample and a perpendicular detection system to enable imaging of optical sections of the samples, which can be living or not. In most embodiments, the SPIM system requires extensive sample preparation to hold the sample in a correct position for imaging. For example, the sample is typically embedded in an agarose cylinder which is submerged in a small chamber filled with an immersion medium, such as water. The technique has been known for over a hundred years, but has only recently found extensive application in imaging biological samples. One disadvantage with the technique is that agarose is not compatible with all biological specimens. The samples are also embedded in vertical cylinders of agarose of limited height in current SPIM systems. This arrangement does not allow for access to the sample during imaging or re-positioning of the sample. The arrangement limits the number of samples that can be imaged since, for example, it is not possible to stack 50 samples in the limited length of the agarose cylinder.
SPIM systems are described, for example, in international patent application No. WO 2004/053558 (Stelzer et al., assigned to the European Molecular Biology Laboratory). This disclosure teaches a microscope in which a thin strip of light (light sheet) illuminates a sample (specimen) and the sample is viewed through a detector. The axis of the detector is situated substantially perpendicular to the direction of an illumination beam. The sample is displaced through the strip of light and the detector records diffused light from the sample or fluorescent light from the sample in a series of images. Three-dimensional images of the sample can be created by the optical sectioning of the sample and then reconstructing the entire image of the sample.
Shroff et al have developed a module for a conventional microscope that is coupled to the translational base of the conventional microscope (International Patent Application No. WO 2012/122027, Shroff et al, assigned to the US). The combination of the module and an inverted microscope enables the same sample to be imaged in two ways that can complement each other.